Multilumen catheters and methods for their use

ABSTRACT

Multilumen catheters are provided. The subject multilumen catheters include a proximal end and a distal end separated by a non-coaxial multilumen tube. The subject catheters are further characterized in that they include a multiport manifold at their proximal ends, where at least two of the ports of the multiport manifold may comprise luer valves. Also provided are systems for use in flushing a vascular site with fluid, usually at least two different fluids, where the subject systems are made up of two multilumen catheters according to the subject invention, where one of the catheters is inserted inside of the other. In addition, kits comprising various components of the subject systems, e.g., at least two different multilumen catheters, are provided. The subject multilumen catheters, systems and kits find use in a variety of different applications in which it is desired to flush a vascular site with at least one and preferably two different fluids, where particular applications of interest include the treatment of vascular lesions.

FIELD OF THE INVENTION

[0001] The field of this invention is atherosclerosis and relatedvascular conditions, and particularly catheter devices used for treatingsuch conditions.

BACKGROUND OF THE INVENTION

[0002] The formation of plaques or lesions (atherosclerotic plaques orlesions), on vascular tissue, such as the inner surface of bloodvessels, aortic valves, etc., is a major component of various vasculardisease conditions. For example, plaques on heart related vascularstructures, e.g., coronary artery intima, heart valves, etc., are oftenimplicated in various heart disease conditions. Likewise, plaques orlesions present on the intima of peripheral vessels, e.g., arteries, areoften implicated in various peripheral vascular disease conditions.

[0003] A variety of different protocols have been developed for treatingdiseases associated with the presence of vascular lesions or plaques.Such treatment methodologies generally involve mechanical removal orreduction of the lesion, and include: bypass surgery, balloonangioplasty, mechanical debridement, atherectomy, valve replacement, andthe like. Despite the plethora of different treatment strategies thathave been developed for the treatment of such vascular diseaseconditions, there are disadvantages associated with each technique, suchas tissue damage, invasiveness, etc. For example, restenosis is a commoncomplication that results in arteries in which lesions have beenmechanically removed.

[0004] As such, there is continued interest in the development of newtreatment protocols for the removal of vascular lesions from vasculartissue, as well as catheter devices that are used in such protocols.

[0005] Literature

[0006] U.S. Patents of interest include: U.S. Pat. Nos. 4,329,994;4,838,881; 5,149,330; 5,167,623; 5,207,648 5,542,937; 6,004,310; and6,013,068. Also of interest are U.S. Pat. Nos.: 4,445,892; 4,573,966;4,610,662; 4,636,195; 4,655,746; 4,824,436; 4,911,163; 4,976,733;5,059,178; 5,090,960; 5,167,628; 5,195,955; 5,222,941; 5,380,284;5,443,446; and 5,462,529. See also: WO 00/03651; WO 01/13985; WO01/15767; WO 01/39783; WO 01/70320; and WO 02/15958; the disclosures ofthe priority documents of which are herein incorporated by reference.

SUMMARY OF THE INVENTION

[0007] Multilumen catheters are provided. The subject multilumencatheters include a proximal end and a distal end separated byan-off-axis or non-coaxial multilumen tube. The subject catheters arefurther characterized in that they include a multiport manifold at theirproximal ends, where at least two of the ports of the multiport manifoldcomprise a mechanism, e.g., a luer valve, for establishing a sealedfluid communication with the lumen of an external tubular member. Alsoprovided are systems for use in flushing a vascular site with fluid,usually at least two different fluids, where the subject systems aremade up of two multilumen catheters according to the subject invention,where one of the catheters is inserted inside of the other catheter in anesting configuration. Catheters so-configured and filled with suchfluids are included in the invention. In addition, kits comprisingvarious components of the subject systems, e.g., at least two differentmultilumen catheters, are provided. In addition, systems comprisingvarious components of the subject systems, e.g., at least two differentmultilumen catheters, are provided. The subject multilumen catheters,systems and kits find use in a variety of different applications inwhich it is desired to flush a vascular site with at least one andpreferably two different fluids, where particular applications ofinterest include the treatment of vascular lesions.

BRIEF DESCRIPTION OF THE FIGURES

[0008] Each of the following figures provide examples diagrammaticallyillustrating aspects of the present invention.

[0009]FIGS. 1A and 1B each provide a representation of an aspirationcatheter according to the subject invention.

[0010]FIGS. 2A, 2B and 2C each provide a representation of a totalocclusion catheter according to the subject invention.

[0011]FIGS. 3A, 3B and 3C each provide a representation of a partialocclusion catheter according to the subject invention.

[0012]FIG. 4 provides a representation of a total occlusion cathetersystem according to the subject invention.

[0013]FIG. 5 provides a representation of a partial occlusion cathetersystem according to the subject invention.

[0014]FIG. 6 shows the distal end of a total occlusion catheter systemflushing a target vascular site in a method according to the subjectinvention.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

[0015] Multilumen catheters are provided. The subject multilumencatheters include a proximal end and a distal end separated by anoff-axis or non-coaxial multilumen tube. The subject catheters arefurther characterized in that they include a multiport manifold at theirproximal ends, where at least two of the ports of the multiport manifoldcomprise a mechanism, e.g., a luer valve, for establishing a sealedfluid communication with the lumen of an external tubular member. Alsoprovided are systems for use in flushing a vascular site with fluid,usually at least two different fluids, where the subject systems aremade up of two multilumen catheters according to the subject invention,where one of the catheters is inserted inside of the other catheter in anesting configuration. Catheters so-configured and filled with suchfluids are included in the invention. In addition, kits comprisingvarious components of the subject systems, e.g., at least two differentmultilumen catheters, are provided. In addition, systems comprisingvarious components of the subject systems, e.g., at least two differentmultilumen catheters, are provided. The subject multilumen catheters,systems and kits find use in a variety of different applications inwhich it is desired to flush a vascular site with at least one andpreferably two different fluids, where particular applications ofinterest include the treatment of vascular lesions.

[0016] Before the subject invention is described further, it is to beunderstood that the invention is not limited to the particularembodiments of the invention described below, as variations of theparticular embodiments may be made and still fall within the scope ofthe appended claims. It is also to be understood that the terminologyemployed is for the purpose of describing particular embodiments, and isnot intended to be limiting. Instead, the scope of the present inventionwill be established by the appended claims.

[0017] It must be noted that, as used in this specification and theappended claims, the singular forms “a,” “an” and “the” include pluralreference unless the context clearly dictates otherwise. Unless definedotherwise all technical and scientific terms used herein have the samemeaning as commonly understood to one of ordinary skill in the art towhich this invention belongs.

[0018] Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit, unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges, and such embodiments are also encompassed within theinvention, subject to any specifically excluded limit in the statedrange. Where the stated range includes one or both of the limits, rangesexcluding either or both of those included limits are also included inthe invention.

[0019] All publications mentioned herein are incorporated herein byreference for the purpose of describing and disclosing components thatare described in the publications that might be used in connection withthe presently described invention.

[0020] Systems as introduced in the Summary of the Invention aredescribed in detail below. The subject multilumen catheters will bedescribed first, both generally and in terms of the figures, followed bya description of the subject systems, kits and representative methods inwhich the catheters, systems and kits find use.

[0021] Multilumen Catheters

[0022] As summarized above, the present invention provides multilumencatheters. Specifically, the subject invention includes three differentmultilumen catheters, which can be used together as a system tosimultaneously flush a vascular site with two distinct fluids. Commonfeatures of each catheter of the subject invention are that they includea proximal end and a distal end separated by an elongated non-coaxialmultilumen tube. By non-coaxial multilumen tube, it is meant a tube thatincludes at least two lumens which are non-coaxial, i.e., they do notshare a common axis. The number of lumens in the multilumen tube mayvary, but generally is 2 to 5, and is often 2 to 4, where in certainembodiments the number is 2 or 3. By elongated, it is meant that thedistance between the proximal and distal ends is sufficient for thecatheter to be inserted or introduced into the vascular system of apatient at a site remote from the vascular lesion that is to be treatedthrough action of the distal end of the catheter, as is known in theart. Catheters intended for intravascular introduction will typicallyhave a length in the range from 50 cm to 200 cm and an outer diameter inthe range from 1 French (0.33 mm; Fr.) to 12 Fr., usually from 3 Fr. to9 Fr. In the case of coronary catheters, the length is typically in therange from 125 to 200 cm, the diameter is preferably below 8 Fr., morepreferably below 7 Fr., and most preferably in the range from 2 Fr. to 7Fr. In certain embodiments, the elongated tubular element has a lengthof from about 80 to 200 cm, usually from about 90 to 180 cm and moreusually from about 90 to 140 cm.

[0023] All of the subject multilumen catheters are further characterizedin that they include a multiport manifold at their proximal ends. Bymultiport manifold is meant a manifold that includes two or more ports(in addition to the attachment structure of the mannifold to theproximal end of the elongated tube of the catheter), where the number ofports in the manifold may range from 2 to 4, but is generally 2 or 3,depending on the particular multilumen catheter. In addition, at leasttwo of the ports of the multiport manifold preferably have luer valvesor analogous means for establishing a sealed fluid communication withthe lumen of an external tubular element or analogous fluid conveyingmeans. In many embodiments, a luer valve is present in these ports,where the valve may be a male or female luer valve. Luer valves aredisclosed in U.S. Pat. Nos. 6,063,062; 6,039,302; 5,954,313; 5,947,954;5,788,215; 5,775,671; 5,738,144; 5,549,651; 5,535,785; 5,474,544;5,441,487; 5,372,143; 5,284,475; the disclosures of which are hereinincorporated by reference. As such, where the multiport manifold is atwo port manifold, each of the two ports in the manifold will typicallyhave a luer valve. Alternatively, where the multiport manifold is athree port manifold, only two of the three ports may have luer valves orall three ports may have luer valves.

[0024] Another common feature of all of the multilumen catheters of thesubject invention is that the elongated multilumen tube is typically apolymeric extruded element, which is made up of one or morebiocompatible polymers that have been extruded to produce thenon-coaxial multilumen tube. Biocompatible polymers of interest include,but are not limited to: polyimide, polyamide, PBAX™, polyethylene,polyisoprene, nylon and the like.

[0025] Although each of the disparate multilumen catheters share theabove common features, there are differences between the differentspecific multilumen catheter designs of the subject invention. As such,each specific type of multilumen catheter of the subject invention,e.g., aspiration, total and partial multilumen catheters, will now bedescribed separately in greater detail.

[0026] Aspiration Catheter

[0027] The first multilumen catheter of the subject invention isidentified herein as the aspiration catheter, as it includes the lumenemployed for aspiration when the catheter is used in a system forflushing a vascular site with fluid. The aspiration catheter ischaracterized by having a proximal end and a distal end separated by anon-coaxial two lumen tube, where a three port manifold is present atthe proximal end. In the three port manifold, two of the ports, and morespecifically the side or offset ports, have luer valves, while thecentral port has a valve capable of opening and closing around a tubularelement, e.g., a catheter, dilator, guidewire, etc., to produce a sealedrelationship with the tubular element. In many embodiments, this elementis a Touhy-Borst valve or analogous structure, where Touhy-Borst valvesare described in U.S. Pat. Nos. 5,795,307 and 5,320,613; the disclosuresof which are herein incorporated by reference.

[0028]FIGS. 1A and B provide a depiction of a representative aspirationcatheter according to the subject invention. In FIG. 1A, aspirationcatheter 10 has proximal end 14 and distal end 12 separated by elongatednon-coaxial two lumen tube 16. The length of elongated tube 16 should belong enough to provide for access of the distal end to the targetvascular site upon introduction into the host, subject or patient at aremote site, and typically ranges from about 80 to 200 cm, usually fromabout 90 to 180 cm and more usually from about 90 to 140 cm. The outerdiameter of the elongate tubular member 16 may vary depending on thetarget vascular site for which it is designed to be used. In otherwords, the outer diameter of the aspiration catheter is selected so asto provide for access of the distal end of the catheter to the vascularsite via the vascular system from the remote point of entry, where theouter diameter typically ranges from about 1.0 to 4.0 mm (3 to 12 Fr),usually from about 1.5 to 3.0 mm (4.5 to 9.0 Fr) and more usually fromabout 1.7 to 2.7 mm (5 to 8 Fr). In the case of coronary catheters, thelength is typically in the range from 125 to 200 cm, the diameter ispreferably below 8 Fr., more preferably below 7 Fr., and most preferablyin the range from 2 Fr. to 7 Fr.

[0029] The aspiration catheter is further characterized in that one ofthe two lumens, generally the larger of the two lumens, opens at thedistal end, thereby providing a fluid entry site for fluid from thetarget vascular site to flow into the lumen. In FIG. 1B, this largerlumen is designated 17. The inner diameter of this lumen at the opendistal end and along the entire length of the tube 16 is sufficient tohouse either a partial or total occlusion multilumen catheter, asdescribed in greater detail below, and remove fluid from the vascularsite at the desired rate, e.g., a rate that provides for substantiallyisometric or isobaric pressure in the vascular site during treatment,through the resultant annular space. This larger lumen 17 is also knownas the aspiration lumen. The inner diameter of the aspiration lumen 17,at least at its distal end and generally along the entire length of theaspiration catheter, is sufficient to provide for adequate flow into thelumen of the catheter, and sometimes ranges from about 0.20 to 2.0,usually from about 0.25 to 1.75 and more usually from about 0.35 to 1.5mm.

[0030] Also present at the distal end of the aspiration catheter 10 is avessel occlusion means 13, where the vessel occlusion means is usuallyan inflatable balloon. The balloon 13 is one that is inflatable to avolume sufficient to substantially occlude the vessel in which theaspiration catheter is positioned, e.g., by pressing against the intimalsurface of the vessel in which the aspiration catheter is positioned.The inflated balloon diameter generally ranges from about 2 to 30 mm,usually from about 5 to 20 mm. The inflated balloon length typicallyranges from about 10 to 30 mm, usually from about 15 to 20 mm. Theballoon is in fluid or gaseous communication with an inflation lumen 19which is the other lumen of the two lumen tube and runs the length ofthe aspiration catheter from the balloon to the proximal end, but doesnot open up at the distal end of the catheter. The inflation lumentypically has an inner diameter that ranges from about 0.1 to 0.5 mm,usually from about 0.2 to 0.4 mm. In certain embodiments, the aspirationcatheter further includes a separate guidewire lumen (not shown).However, in many embodiments, a separate guidewire lumen is not present.

[0031] At the proximal end 14 of aspiration catheter 10 is three portmanifold 18. Three port manifold 18 includes side or offset ports 11 aand 11 c, as well as central port 11 b. One of the offset ports, e.g.,11 a is in fluid communication with the smaller lumen 19 and is attachedto a balloon inflation means, e.g., a syringe filled with gas or fluid,during use. The other offset port, e.g., 11 c, is in fluid communicationthe larger aspiration lumen 17 and is attached to a source of negativepressure, e.g., a vacuum, during use. Offset ports 11 a and 11 c arefurther characterized in having or being in communication with luervalves 15 a and 15 c, respectively. In many embodiments, luer valves 15a and 15 c are female luer valves. Central port 11 b is in fluidcommunication with the aspiration lumen 17 and provides the point ofaccess for the total and partial occlusion catheters, described ingreater detail below. As such, in the manifold 18 of the aspirationcatheter, two of the ports of the manifold, specifically the centralport and one of the offset ports, are in fluid communication with theaspiration lumen 17. Central port 11 b is characterized by the presenceof Touhy-Borst valve 15 b or an analogous structure. Touhy-Borst valvessuitable for use in medical devices, e.g., catheters, are described inU.S. Pat. No. 5,320,613 and 5,795,307.

[0032] Also present on the catheter shown in FIG. 1A is a strain relief18 a. The strain relief protects the proximal end of tube 16 from damageand gives strength to the transition between the tube and manifold 18.The strain relieve locally increases the stiffness of tube 16 to providea moderated step-wise increase in stiffness from the relatively moreflexible tube to the stiffer manifold member. The length of the strainrelieve may varies from 5 to 40 mm, but is usually 20 to 30 mm inlength. Suitable materials for strain relief 18 a include fluorinatedethylene-propylene or a similar medical grade polymer.

[0033] The embodiment shown in FIG. 1A includes three-way stop cocksattached to each of the offset ports. These provide for further controlof fluid flow into the lumens of the device and/or the introduction oftwo separate fluids into the same lumen of the device, e.g., an imagingsolution into the aspiration lumen and aspiration of fluid through theaspiration lumen, depending on the state of the three way stop-cock.

[0034] For convenience during use of the aspiration catheter, each ofthe ports of the three port manifold may be uniquely identified, e.g.,color coded, so that it is readily apparent as to the element that theport should be connected during use of the device, e.g. vacuum source,balloon inflation means, etc. For example, one of the offset ports mayhave a yellow band, one may have a green band and one may have a redband, thereby uniquely identifying the ports of the three port manifold.

[0035] Total Occlusion Multilumen Catheter

[0036] Also provided by the subject invention are multilumen cathetersthat are designed to be inserted inside the aspiration lumen and used toflush a vascular site that is characterized by the presence of a totalvascular occlusion, e.g., as shown in FIG. 6 described in greater detailbelow. These catheters are identified herein as total occlusioncatheters. In general, the total occlusion catheters are characterizedin that the multilumen tube separating the proximal and distal ends is atwo lumen tube. These total occlusion catheters are furthercharacterized in that the multiport manifold is preferably a two portmanifold, where both of the ports have luer valves. In certainembodiments, the multilumen total occlusion aspiration catheter furtherincludes a guidewire lumen.

[0037]FIGS. 2A and B and C each provide a representation of a totalocclusion catheter according to the subject invention. As shown in FIG.2A, total occlusion catheter 20 includes proximal end 24 and distal end22 separated by elongated tubular member 26. Elongated tubular member 26is sufficiently long to provide for access of the distal end to thetarget vascular site upon introduction into the host vascular system viaa remote entry site of the vascular system. Typically, the length ofelongate member 26 ranges from about 90 to 210 cm, usually from about100 to 190 cm and more usually from about 110 to 150 cm. The outerdiameter of the tubular member 26 is such that it may be slidablypositioned inside the aspiration lumen of the aspiration catheter, asdescribed above. Typically, the outer diameter of element 26 ranges fromabout 0.5 to 2.0 (1.5 to 6.0 Fr), usually from about 0.8 to 1.6 mm (2.5to 5 Fr).

[0038] Tubular member 26 is a two lumen tubular member, where the lumensof the catheter are non-coaxial. Each of the lumens, 25 and 27, open atthe distal end of catheter 20. One of the lumens is designed to carry afirst fluid and the other is designed to carry a second fluid. In manyembodiments, the first fluid is a dissolution fluid and the second fluidis a dissolution fluid attenuating fluid, as described in greater detailbelow. The configuration of the each of the lumens in the embodimentshown in FIG. 2A can be seen in FIG. 2B, which is a cross section oftubular member 26 taken at line A-A shown in FIG. 2A. As can be seen inthe representative embodiment, lumen 25 has a substantially circularconfiguration while lumen 27 has a crescent configuration so as to sharea common wall or border with a substantial portion of lumen 25, where by“substantial portion” is meant at least 25%, usually at least 35% andmore usually at least 50% of the circumference of lumen 25, where incertain embodiments this portion may be much higher, e.g., 60%, 75% etc.Lumen 25 is typically employed for conveying the dissolution fluid whilelumen 27 is typically employed for conveying the dissolution fluidattenuating fluid during use. In FIG. 2C, the cross sectional view showa three lumen total occlusion catheter, where lumen 25 a is employed fordissolution solution, lumen 27 is employed for dissolution fluidattenuating fluid delivery and lumen 29 is the guidewire lumen.

[0039] The inner diameter of lumen 25 typically ranges from about 0.2 to1.0 mm, usually from about 0.2 to 0.7 mm and more usually from about 0.3to 0.4 mm, so as to provide for a cross-sectional area of about 0.03 to0.8 mm², usually from about 0.03 to 0.4 mm² and more usually from about0.07 to 0.2 mm². The cross-sectional area of lumen 27 typically rangesfrom about 0.03 to 0.8 mm², usually from about 0.03 to 0.4 mm² and moreusually from about 0.07 to 0.2 mm². While the configuration of FIG. 2Bshows a circular and crescent shaped lumen, other configurations arealso possible, e.g., two circular lumens, to semicircular lumens, etc.

[0040] Also present on the preferred total occlusion catheter atproximal end 24 is two port manifold 28. Two port manifold 28 includesside or offset port 21 a and central port 21 b. Port 21 a includesfemale luer valve 23 a while port 23 b includes high pressure femaleluer valve 23 b. During use, side or offset port 21 a is typically influid. communication with a source of dissolution fluid attenuatingfluid, e.g., buffer, while central port 23 b is typically in fluidcommunication with a source of dissolution fluid, e.g., acid solution.

[0041] Also present on the catheter shown in FIG. 2A is a strain relief28 a. It functions as described in connection with strain relief 18 a.In the embodiment shown in FIG. 2A, also present is three-way stop cockattached to the central port which provides for further control of fluidflow into the central lumens of the device, the introduction of twoseparate fluids into the same lumen of the device and/or theintroduction of separate fluids for intermittent flushing, e.g. withheparinized saline, typically used to keep lumens clear and preventclotting.

[0042] For convenience during use of the aspiration catheter, each ofthe ports of the two port manifold may be uniquely identified, e.g.,color coded, so that it is readily apparent as to the element that theport should be connected during use of the device, e.g. dissolutionfluid reservoir, dissolution fluid attenuating fluid reservoir, etc. Forexample, one of the offset ports may have a yellow band and one may havea red band, thereby uniquely identifying the ports of the manifold.

[0043] Partial Occlusion Catheter

[0044] Also provided by the subject invention are multilumen cathetersthat are designed to be inserted inside the aspiration lumen and used toflush a vascular site that is characterized by the presence of a partialvascular occlusion. These catheters are identified herein as partialocclusion catheters. In general, the partial occlusion catheters arecharacterized in that the multilumen tube separating the proximal anddistal ends is a three lumen tube. These partial occlusion catheters arefurther characterized in that the multiport manifold is a three portmanifold, where each of the ports has a luer valve or analogousstructure. In addition to the above features, the partial occlusioncatheter also includes a balloon or analogous vessel occlusion means atits distal end and multiple ports proximal to the balloon, where aportion of these infusion ports are in fluid communication with one ofthe lumens and the remainder are in fluid communication with another ofthe lumens. In certain embodiments, the partial occlusion catheters ofthe subject invention further include a guidewire lumen, bring the totalnumber of lumens in the partial occlusion catheter to four.

[0045]FIGS. 3A, B and C provide a representation of a partial occlusioncatheter according to the subject invention. As shown in FIG. 3A,partial occlusion catheter 30 includes distal end 32 and proximal end 34separated by three lumen tube 36. The length of the tubular member 36generally ranges from about 90 to 250 cm, usually from about 100 to 230cm and more usually from about 110 to 190 cm. The outer diameter of thetubular member 36 is such that the partial occlusion catheter 30 may beslidably positioned in the aspiration lumen of the aspiration catheter.As such, the outer diameter of tubular member 36 typically ranges fromabout 0.5 to 2.0, usually from about 0.8 to 1.6 mm.

[0046] Located at the distal end of catheter 30 is balloon 31 oranalogous occlusion means. The balloon is generally one that isinflatable to a diameter ranging from about 2 to 15 mm, usually about 5to 10 mm, and typically has a length of from about 10 to 30 mm, usuallyfrom about 15 to 20 mm. Proximal to the balloon 31 are a series of ports43, 45 and 47 which provide for fluid transfer between the outside oftube 36 and the lumens located inside the device. Typically, ports 43and 45 are in fluid communication with a first lumen inside the tube 36that is carrying dissolution fluid attenuating fluid while port 47 is influid communication with the lumen of the device carrying thedissolution fluid. The diameter of the infusion ports may vary, buttypically ranges from about 0.2 to 1.2, usually from about 0.4 to 1.0and more usually from about 0.5 to 0.8 mm.

[0047] A representative configuration of the three lumens of multilumentube 36 is shown in FIG. 3B, which shows the cross section of tube 36taken along line A-A as shown in FIG. 3A. As shown in FIG. 3B, lumen 37has a substantially circular cross section, while lumens 39 and 41together make up a crescent shape that shares a border with lumen 37that extends for a substantial portion of the perimeter of lumen 37. Thecrescent shape made through combination of lumens 39 and 41 is dividedto provide for distinct lumens 39 and 41. The diameter of lumen 37typically ranges from about 0.02 to 1.0 mm, usually from about 0.2 to0.7 mm and more usually from about 0.3 to 0.4 mm to provide across-sectional area ranging from about 0.03 to 0.8 mm², usually fromabout 0.03 to 0.4 mm². The cross sectional area of lumen 39 typicallyranges from about 0.03 to 0.8 mm², usually from about 0.03 to 0.4 mm²while the cross-sectional area of lumen 41 typically ranges from about0.05 to about 0.3, usually from about 0.1 to about 0.2. In manyembodiments, lumen 37 conveys dissolution fluid attenuating fluid, e.g.,buffer, and/or provides for guidewire use, lumen 39 conveys dissolutionfluid, e.g., acid, and lumen 41 conveys inflation medium, e.g., gas orfluid, to the balloon. While one type of configuration of the variouslumens is shown, other non-coaxial configurations are also possible,e.g., three separate circles, a circle and two distinct crescent shapes,etc., where all of these potential configurations are within the scopeof the invention. FIG. 3C provides a cross-section view of an embodimentthat includes a guidewire lumen. As such, in FIG. 3C one can see theballoon lumen 41, the dissolution fluid and dissolution fluid conveyancelumens, 39 and 37 a, as well as the guidewire lumen 42.

[0048] Located at the proximal end 34 of catheter 30 is three portmanifold 38. Three port manifold 38 includes two offset or side ports 33a and 33 c, which flank central port 33 b. Each of the ports includes afemale luer valve, 35 a, 35 b and 35 c. The central port 33 b istypically in fluid communication with a dissolution fluid attenuatingfluid source during use. Offset port 33 a is typically in fluidcommunication with a source of dissolution fluid. Offset port 33 c istypically in fluid communication with a balloon inflation means, e.g., asyringe filled with a gas or liquid.

[0049] Also present on the catheter shown in FIG. 3A is a strain relief38 a. It functions in the manner of strain relief 18 a and 28 a.

[0050] In the embodiment shown in FIG. 3A, also present are three-waystop cocks attached to each of the offset ports, which elements providefor further control of fluid flow into the lumens of the device, theintroduction of two separate fluids into the same lumen of the deviceand/or the introduction of separate fluids for intermittent flushing,e.g. with heparinized saline, typically used to keep lumens clear andprevent clotting, depending on the state of the three way stop-cock.

[0051] For convenience during use of the aspiration catheter, each ofthe ports of the three port manifold may be uniquely identified, e.g.,color coded, so that it is readily apparent as to the element that theport should be connected during use of the device, e.g. vacuumdissolution fluid, dissolution fluid attenuating fluid, ballooninflation means, etc.

[0052] Systems

[0053] Also provided by the subject invention are systems for flushing avascular site with two different fluids. By flushing a vascular site ismeant introducing fluid into and removing fluid from a vascular site atsubstantially the same time such that the vascular site remainssubstantially stable in terms of pressure, e.g., is isobaric, where thepressure changes that occur in the vascular site do not exceed inmagnitude a value of about 50 mm Hg and usually do not exceed about 30mm Hg. Accordingly, maximum pressure will typically remain below about400 mm Hg, preferably about 100 mm Hg.

[0054] The subject systems are characterized by having an aspirationcatheter and one of the total or partial occlusion catheters of thesubject invention in a nested configuration, such that the total orpartial occlusion catheter is slidably positioned inside the aspirationlumen of the aspiration catheter. FIG. 4 provides a representation of asystem designed for use with a total occlusion which is made up of atotal occlusion catheter 20 inserted into the aspiration lumen of anaspiration catheter. FIG. 5 provides a representation of a systemdesigned for use in the treatment of a partial occlusion, where thesystem is made up of a partial occlusion catheter inserted into theaspiration lumen of an aspiration catheter. Because the central manifoldport of the aspiration catheter may have a Touhy-Borst valve, a fluidseal can be produced at the interface between the aspiration manifoldcentral port and the outer surface of the partial or total occlusioncatheter when inserted into the aspiration lumen of the aspirationcatheter.

[0055] In using the total occlusion catheter system of the subjectinvention, one of the offset ports of the aspiration manifold is oftenin fluid communication with a syringe balloon inflation means and theother offset port of the aspiration manifold is in fluid communicationwith a vacuum source to provide the force for removing fluid from thevascular site via the aspiration lumen. The central port of the totalocclusion manifold is in fluid communication with a source ofdissolution fluid, e.g., an ENDoFLATOR®, etc., while the offset port ofthe total occlusion manifold is in fluid communication with a source ofdissolution fluid attenuating fluid, e.g., an ENDoFLATOR®, etc.

[0056] In using the partial occlusion catheter system according to thesubject invention, one of the offset ports of the aspiration manifold isoften in fluid communication with a balloon inflation mechanism, e.g., afluid or gas filled syringe, and the other offset port of the aspirationmanifold is in fluid communication with a vacuum source. The centralport of the partial occlusion manifold is in fluid communication with asource of dissolution fluid attenuating fluid, e.g., an ENDoFLATOR®filled with dissolution fluid attenuating fluid, while one of the offsetports is in fluid communication with a source of dissolution fluid, e.g.an ENDoFLATOR® filled with dissolution fluid, and the other offset portis in fluid communication with a balloon inflator, e.g. a fluid or gasfilled syringe. In use, each of the catheters are filled with therespective solutions for which sources are provided. Furthermore,balloons provided will be at least partially filled, together withadjacent feed lumen in use. The aspiration lumen may also be subject toat least partial vacuum.

[0057] Methods

[0058] The subject systems find use in applications where it is desiredto simultaneously flush a vascular target site with two differentfluids. As mentioned above, by flush it is meant that the fluid isintroduced into the vascular site and removed from the vascular site isaccomplished in manner such that the vascular site remains atsubstantially constant pressure. However, the pressure throughout thetreatment site is predicted to be, on average, lower than the backbleedpressure, i.e., the blood pressure on the proximal side of theaspiration catheter balloon. While the subject systems can, inprinciple, be employed to flush a vascular site with any two fluids,they are particularly suited for use in applications where chemicaltissue ablation at a target vascular site is desired. As such, thesubject systems find particular use in the treatment of vascular lesionsor obstructions, where the target lesions or obstructions may beorganic, inorganic or composite structures of both organic and inorganiccomponents. In such embodiments, the systems are used to flush thetarget vascular site, and therefore the lesion or obstruction locatedtherein, with a dissolution fluid and a dissolution fluid attenuatingfluid.

[0059] In these embodiments of the subject methods, the first step isgenerally to provide for an entry site for the catheter into thevascular system of the host. Entry is typically provided by placement ofan introducer sheath at a convenient location, e.g. leg etc., as isknown in the art. A guidewire is then inserted through the entry sheathand its distal end is placed at the target vascular site. The aspirationcatheter with a dilator present in the central lumen is then moved overthe guidewire, where the guidewire generally passes through the centrallumen, so that the distal end of the aspiration catheter reaches thetarget vascular site. Following placement of the distal end of theaspiration catheter at the target vascular site and subsequentdeployment of the vascular occlusion means, the dilator is removed andreplaced with either the partial or total occlusion catheter insertedthrough the Touhy-Borst valve of the aspiration manifold central portand into the aspiration lumen. This catheter insert is then movedthrough the lumen, optionally over the guidewire if still present, untilthe distal end of the insert is beyond the distal end of the aspirationcatheter. In many embodiments, the distal end of the insert will extendsome distance beyond the distal end of the aspiration catheter, wherethis distance typically does not exceed about 20 cm and usually does notexceed about 5 mm.

[0060] Upon positioning of the catheter system as described above anddeployment of any vascular occlusion means, the dissolution fluid anddissolution fluid attenuating fluid are introduced into the vascularsite via the appropriate lumens inside the catheter insert and fluid isremoved from the vascular site via the aspiration lumen of theaspiration catheter, and specifically through the annular space presentin the system bordered by the inner wall of the aspiration lumen and theouter wall of the catheter insert. The nature of the dissolution fluidand the dissolution fluid attenuating fluid necessarily depends on thenature of the target lesion to be treated. For example, for organicmatter comprising lesions, organic matter dissolution fluids (and theircompanion attenuating fluids) are of interest, such as those describedin U.S. patent application Ser. No. 09/528,576; the disclosure of whichis herein incorporated by reference. In other embodiments where thetarget lesion comprises inorganic matter, acidic dissolution solutionsand their companion buffer attenuating fluids are of interest, such asthose described in WO 00/03651; the disclosure of the priority documentof which is herein incorporated by reference. See e.g., WO 00/03651; WO01/13985; WO 01/15767; WO 01/39783; WO 01/70320; and WO 02/15958; thedisclosures of the priority documents of which are herein incorporatedby reference.

[0061] In many embodiments, the dissolution fluid employed in thesubject methods is an inorganic matter dissolution solution. In many ofthese embodiments, the inorganic matter dissolution fluid is an acidicdissolution fluid. A variety of different types of acidic dissolutionsolutions may be employed in the subject methods. The acidic treatmentsolutions that find use in the subject methods generally have a pH ofless than about 6.5, where the pH is usually less than about 4.0 andmore usually less than about 3.0. In many preferred embodiments, the pHranges from 0 to 2, and usually 0 to 1. The acidic treatment solutioncan include a number of different types of acids, where the acids may ormay not include a hydrocarbon moiety, i.e., a hydrogen bonded directlyto a carbon atom. Suitable acids that lack a hydrocarbon moiety includehalogen acids, oxy acids and mixtures thereof, where specific acids ofinterest of this type include, but are not limited to, hydrochloric,nitric, sulfuric, phosphoric, hydroboric, hydrobromic, carbonic andhydroiotic acids. For such acids, the acid can be a concentrated acid,or can be diluted. Upon dilution, the concentration of an inorganic acidwill generally be from about 10 N to about 0.01 N, preferably between 5N to 0.1 N. Also of interest are acids that include a hydrocarbonmoiety, where such acids include, but are not limited to, any organicacid of one to six (C₁ to C₆) carbons in length. Organic acids of thistype include, but are not limited to, formic, acetic, propionic, maleic,butanoic, valeric, hexanoic, phenolic, cyclopentanecarboxylic, benzoic,and the like. For an organic acid, the acid can be in concentrated form,or can be diluted. The acidic treatment solution can be composed ofeither a monobasic or a polybasic acid. Acids are “monobasic” when theyhave only one replaceable hydrogen atom and yield only one series ofsalts (e.g., HCl). Acids are “polybasic” when they contain two or morehydrogen atoms which may be neutralized by alkalies and replaced byorganic radicals.

[0062] In many embodiments of the subject invention, the acid solutionis hypertonic, by which is meant that the osmolarity of the solution isgreater than that of whole blood, i.e. the osomolarity is greater than300 mosmol. The solution may be rendered hypertonic by including anyconvenient component or components in the solution that provide for thedesired elevated osmolarity.

[0063] Any convenient agent that is capable of increasing the osmolarityof the solution may be employed, where suitable agents include salts,sugars, and the like. In many embodiments, the agent that is employed torender the solution hypertonic is one or more, usually no more thanthree, and more usually no more than two, different salts. Generally,the salt concentration in these embodiments of the solution is at leastabout 100 mosmol, usually at least about 200 mosmol and more usually atleast about 300 mosmol, where the concentration may be as high as 3000mosmol or higher, depending on the particular salt being employed torender the solution hypertonic, where the solution may be saturated withrespect to the salt in certain embodiments. Salts that may be present inthe subject solutions include: NaCl, MgCl₂, Ringers, etc. where NaCl ispreferred in many embodiments.

[0064] Of particular interest in many embodiments is the use of ahydrogen chloride solution. In hydrogen chloride solutions that find usein the subject invention, the concentration of HCl in the solutionranges from about 0.001 to 1.0 N, usually from about 0.01 to 1.0 N andmore usually from about 0.1 to 1.0 N. In many embodiments, the hydrogenchloride solution will further include one or more salts which make thesolution hypertonic, as described above. In certain preferredembodiments, the salt is NaCl, where the concentration of NaCl in thesolution is at least 0.05 M, usually at least 0.10 M, and more usuallyat least 0.15 M, where the concentration may be as high as 0.25 M orhigher. In certain embodiments, the solution will be saturated withNaCl.

[0065] Of particular interest are aqueous hydrogen chloride solutionsthat consist of water, hydrogen chloride and NaCl. The concentration ofhydrogen chloride in these solutions of particular interest ranges fromabout 0.01 to 1.0 N, usually from about 0.05 to 0.5 N and more usuallyfrom about 0.075 to 0.25 N. The concentration of NaCl in these solutionsof particular interest ranges from about 0.05 to 0.25 M, usually fromabout 0.05 to 0.10 M.

[0066] In certain embodiments, one or more of the delivery fluids ispresent at a temperature that is less than room temperature. Forexample, in certain embodiments, the one or more treatment solutions, asdescribed above, is present at a temperature ranging from about 0 toabout 20° C., sometimes from about 0 to 15° C., e.g., from about 0 to10° C. Such embodiments include applications where it is desired tolimit restinosis by employing reduced temperature, e.g., cold,solutions.

[0067]FIG. 6 provides a representation of the distal end of a totalocclusion catheter system flushing a target vascular site with an acidicdissolution fluid and a buffer dissolution fluid attenuating fluid. InFIG. 6, the target vascular site 61 is shown with total vascularocclusion 62. The distal end of total occlusion catheter system 60 isshown with aspiration catheter 10 and total occlusion catheter 20extending beyond the end of aspiration catheter 10. Acidic dissolutionfluid 63 exits lumen 25 while buffer dissolution fluid attenuating fluid64 exits lumen 27. Fluid comprising acid, buffer and dissolved plaque,i.e., 65, is withdrawn from the vascular site by the annular opening ofthe aspiration lumen of the aspiration catheter.

[0068] The target vascular site is flushed with the dissolution anddissolution fluid attenuating fluids for a period of time sufficient toresult in the desired amount of treatment, e.g., target lesion sizereduction, enhancement or establishment of fluid flow through the targetsite, etc. Following the desired amount of treatment, the system isremoved from the host. More specific detail regarding the methods inwhich the subject systems find use can be found in U.S. Pat. No.09/528,576; the disclosure of which is herein incorporated by reference;and publication no. WO 00/03651 the disclosure of the priority documentof which is herein incorporated by reference.

[0069] In certain embodiments, external energy is applied to the targetaortic valve to promote mechanical break-up of the calcified depositsinto particles or debris that can be easily removed from the vascularsite. Any means of applying external energy to the aortic valve may beemployed. As such, jets or other such means the device which are capableof providing varying external forces to the target deposits cause thetarget deposit to break up or disrupt may be employed. Of particularinterest in many embodiments is the use of sonic energy, e.g.,ultrasound. Another means that may be employed to apply external energyto the lesion during the dissolution process is to use a mechanicalmeans of applying external energy. Mechanical means of interest includemoving structures, e.g. rotating wires, guidewires, which physicallycontact the target lesion and thereby apply physical external energy tothe target lesion.

[0070] Kits

[0071] Also provided by the subject invention are kits for use influshing a vascular site with two fluids. The subject kits at leastinclude the components of a partial occlusion or total occlusioncatheter system according to the subject invention. As such, the kitsinclude an aspiration catheter and at least one of a partial occlusioncatheter and a total occlusion catheter. In many embodiments, the kitsinclude both a partial occlusion catheter and a total occlusioncatheter. The subject kits may also include a dissolution fluid and/ordissolution fluid attenuating fluid, or components/precursors thereof,where representative dissolution fluids and dissolution fluidattenuating fluids are disclosed above. The dissolution fluids anddissolution fluid attenuating fluids or component(s) thereof are presentin the kit in a suitable container, e.g., a bottle, pouch, fluid filledEndeflator, etc. which is capable of serving as a storage vessel for thethis component of the kit and, preferably, capable of preserving thesterility of this component of the kit, as this component of the kit ispreferably sterile, e.g., medical grade.

[0072] The kits of the subject invention may also include a number ofdifferent optional components, which components may find use in methodsin which the subject kit components are employed. One optional componentthat may be present in the subject kits is a guidewire. Any convenienttype of guidewire may be present, where a number of different guidewiresare known to those of skill in the art. Guidewires of interest includethose described in U.S. Pat. Nos. 6,007,514; 5,980,471; 5,957,865;5,938,609; 5,931,819; 5,916,178; 5,908,395; 5,902,254; 5,865,767;5,827,201; 5,788,654; 5,772,609; 5,769,796; 5,755,695; 5,749,837;5,682,897; 5,660,180; 5,636,642; 5,606,981; 5,599,492; 5,596,996;5,558,093; 5,546,948; 5,520,189; 5,507,301; 5,497,782; D363,776;5,460,187; 5,441,497; 5,437,288; 5,427,118; 5,421,349; 5,411,033;5,409,015; 5,368,035; 5,341,818; 5,339,833; 5,313,967; 5,303,714;RE34,466; 5,265,622; 5,238,005; 5,184,621; 5,167,239; 5,147,317;5,144,959; 5,111,829; 5,107,852; 5,095,915; 5,095,911 5,084,022;5,069,226; 5,063,935; 4,966,163; 4,953,553; 4,875,489; 4,827,941;4,811,743; 4,676,249; 4,534,363; 4,080,706 and 4,003,369; thedisclosures of which are herein incorporated by reference. Also ofinterest are dilators for use in creating entries into the vascularsystem of the host.

[0073] Additional optional components that may be present in kits of thesubject invention include various fluids and solutions in addition tothe dissolution fluid and dissolution fluid attenuating fluid describedabove. Additional fluids that may be present include: organic matterdissolution fluids, wash or rinsing fluids, imaging agent fluid mediumsthat include an imaging agent, such as a non-ionic imaging agents, e.g.,CONRAY™, OXILAN™, fluids containing one or more pharmacological agents,e.g., agents that promote healing, reduce inflammation, and the like;etc.

[0074] Other components that may be present in the subject kits includeone or more additional components and accessories for use with the fluiddelivery means present in the kit, including tubing for connecting thevarious catheter components with fluid reservoirs, syringes, pumps,etc., connectors, stop-cocks, dilators, insertion sheaths, vacuumregulators, negative pressure or vacuum generators/sources, luer valveadapters, etc.

[0075] In addition to above mentioned components, the subject kitstypically further include instructions for using the components of thekit to flush a vascular site with two different fluids, e.g., to flush avascular site with a dissolution fluid and a dissolution fluidattenuating fluid. The instructions for practicing the subject methodsare generally recorded on a suitable recording medium. For example, theinstructions may be printed on a substrate, such as paper or plastic,etc. As such, the instructions may be present in the kits as a packageinsert, in the labeling of the container of the kit or componentsthereof (i.e., associated with the packaging or subpackaging) etc. Inother embodiments, the instructions are present as an electronic storagedata file present on a suitable computer readable storage medium, e.g.CD-ROM, diskette, etc. In yet other embodiments, the actual instructionsare not present in the kit, but means for obtaining the instructionsfrom a remote source, e.g. via the internet, are provided. An example ofthis embodiment is a kit that includes a web address where theinstructions can be viewed and/or from which the instructions can bedownloaded. As with the instructions, this means for obtaining theinstructions is recorded on a suitable substrate.

[0076] It is evident from the above discussion that the catheters andsystems that are made up of the same provide a reliable and convenientway to flush a target vascular site with two different fluids. Becausethe catheter devices have a design that allows them to be produced viaextrusion technology using polymeric materials, they may be economicallyproduced and the number of different working elements is kept to aminimum. In view of these factors and such others discussed above, thesubject kits represent a significant contribution to the art.

[0077] All publications and patent applications cited in thisspecification are herein incorporated by reference as if each individualpublication or patent application were specifically and individuallyindicated to be incorporated by reference. The citation of anypublication is for its disclosure prior to the filing date and shouldnot be construed as an admission that the present invention is notentitled to antedate such publication by virtue of prior invention.

[0078] Although the foregoing invention has been described in somedetail by way of illustration and example for purposes of clarity ofunderstanding, it is readily apparent to those of ordinary skill in theart in light of the teachings of this invention that certain changes andmodifications may be made thereto without departing from the spirit orscope of the appended claims.

1. A multilumen catheter comprising: (a) a proximal end; (b) a distalend; and (c) a multiport manifold located at said proximal end, wherein:(i) said multiport manifold comprises at least two ports having luervalves; and (ii) said proximal and distal ends are separated by anon-coaxial multilumen tube.
 2. The multilumen catheter according toclaim 1, wherein said multiport manifold comprises three ports and saidmultilumen tube comprises two lumens.
 3. The multilumen catheteraccording to claim 2, wherein a first port of said three port manifoldcomprises a Touhy-Borst valve and the remaining two ports of said threeport manifold comprise luer valves.
 4. The multilumen catheter accordingto claim 3, wherein a vascular occlusion mechanism is associated withsaid distal end.
 5. The multilumen catheter according to claim 4,wherein said vascular occlusion mechanism is a balloon.
 6. Themultilumen catheter according to claim 4, wherein the diameter of one ofsaid two lumens is substantially larger than the diameter of the otherof said two lumens.
 7. The multilumen catheter according to claim 6,wherein two of said ports of said three port manifold are in fluidcommunication with said lumen of larger diameter.
 8. The multilumencatheter according to claim 7, wherein one of said ports in fluidcommunication with said larger diameter lumen is said port comprising aTouhy-Borst valve.
 9. The multilumen catheter according to claim 1,wherein said multiport catheter is a two port catheter and saidmultilumen tube comprises two lumens.
 10. The multilumen catheteraccording to claim 9, wherein said luer valves are female luer valves.11. The multilumen catheter according to claim 9, wherein one of saidtwo lumens has a substantially circular cross section while the other ofsaid two lumens has a substantially non-circular cross section.
 12. Themultilumen catheter according to claim 1 1, wherein said non-circularcross section lumen has a crescent shaped cross-section.
 13. Themultilumen catheter according to claim 12, wherein said lumen having acrescent shaped cross section is positioned in said tube so as to beadjacent to at least 50% of the perimeter of said lumen having asubstantially circular cross-section.
 14. A multilumen catheteraccording to claim 1, wherein said multiport manifold is a three portmanifold and said multilumen tube comprises three lumens.
 15. Themultilumen catheter according to claim 14, wherein each of said threeports of said three port manifold comprises a luer valve.
 16. Themultilumen catheter according to claim 15, wherein said luer valves arefemale luer valves.
 17. The multilumen catheter according to claim 14,wherein a vascular occlusion mechanism is associated with said distalend.
 18. The multilumen catheter according to claim 17, wherein saidvascular occlusion mechanism is a balloon.
 19. The multilumen catheteraccording to claim 14, wherein one of said lumens of said three lumentube has a substantially circular cross section while the remaining twolumens have substantially non-circular cross sections.
 20. Themultilumen catheter according to claim 19, wherein said cathetercomprises at least two ports at said distal end to provide for the exitof fluid from said lumen having a substantially circular cross section.21-43. (Canceled).
 44. A system for flushing a vascular site, saidsystem comprising: (I) a first two lumen catheter comprising: (A) aproximal end; (B) a distal end; and (C) a three port manifold located atsaid proximal end, wherein: (i) said three port manifold comprises atleast two offset ports having luer valves and a central port comprisinga Touhy-Borst valve; and (ii) said proximal and distal ends areseparated by a non-coaxial two lumen tube; and (II) a second multilumencatheter inserted inside of one of said two lumens of said first twolumen catheter; wherein said second multilumen catheter is a catheterselected from the group consisting of: (A) a two lumen cathetercomprising: (i) a proximal end; (ii) a distal end; and (iii) a two portmanifold located at said proximal end, wherein each port of said twoport manifold comprises a luer valve; and said proximal and distal endsare separated by a non-coaxial two lumen tube; and (B) three lumencatheter comprising: (i) a proximal end; (ii) a distal end; and (iii) athree port manifold located at said proximal end, wherein, each port ofsaid three port manifold comprises a luer valve; and said proximal anddistal ends are separated by a non-coaxial three lumen tube. 45-57.(canceled).
 58. A kit for using in flushing a vascular site with fluid,said kit comprising: (I) a first two lumen catheter comprising: (A) aproximal end; (B) a distal end; and (C) a three port manifold located atsaid proximal end, wherein: (i) said three port manifold comprises atleast two offset ports having luer valves and a central port comprisinga Touhy-Borst valve; and (ii) said proximal and distal ends areseparated by a non-coaxial two lumen tube; and (II) at least one secondmultilumen catheter selected from the group consisting of: (A) a twolumen catheter comprising: (i) a proximal end; (ii) a distal end; and(iii) a two port manifold located at said proximal end, wherein: (a)each port of said two port manifold comprises a luer valve; and (b) saidproximal and distal ends are separated by a non-coaxial two lumen tube;and (B) a three lumen catheter comprising: (i) a proximal end; (ii) adistal end; and (iii) a three port manifold located at said proximalend, wherein; (a) each port of said three port manifold comprises a luervalve; and (b) said proximal and distal ends are separated by anon-coaxial three lumen tube.